Combined gas chromatographic mass spectrometric methods previously developed to assay biogenic amines in various biological media have been employed to assess total body turnover of norepinephrine (sum NE) and dopamine (sum DA) in human subjects and rats. We have also compared changes in these chemicals after a number of pharmacological manipulations in rats. The aim of these animal studies was to gain an insight into how these pharmacological treatments influence brain catecholamines in depression, schizophrenia, and hyperactivity in children. (1) We have continued to gather additional supportive data that suggest a tendency for sum NE to be elevated in major depression. We have also observed a positive correlation between urinary-free cortisol, and urinary NE and vanillmandelic acid (VMA), a major metabolite of NE in the periphery in humans. (2) Total body NE and DA turnover was assessed in both hyperactive children and adults after several pharmacological manipulations. The results indicated a correlation between therapeutic benefits and changes in both sum NE and DA irrespective of the direction of change. (3) The effects of 4 commonly used antidepressant treatments on rat peripheral and central catecholamines were evaluated. A good correlation between the effects of these drugs and sum NE and sum DA in humans and rats was observed. It is suggested that because of this correlation, changes in the rat brain amines observed probably resemble the changes these treatments induce in the human brain. The treatments were chronic zimelidine, desipramine, electroconvulsion, and lithium. (4) We are currently attempting to reproduce our initial study on DA and NE turnover in schizophrenia and hope to also include patients with tardive dyskinesia. (5) The above methods were employed in the evaluation of central and peripheral production of catecholamine in Norrie Disease.